反应详情

A solution of 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (0.252 mmol) in dioxane (1.5 mL) was treated with 5-bromo-2,3-dihydro-1H-indene (0.252 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (10 mg), and 2M aq potassium carbonate (0.756 mmol). The reaction mixture was purged with nitrogen, sealed, and irradiated in a microwave (Biotage Initiator) at 150° C. for 15 min. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH˜4 using 1N aq HCl and was extracted with dichloromethane. The resulting organic phase was treated with Si-Thiol (Silicycle, 20 mg), dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC (35-65% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions from the HPLC were combined, adjusted to pH˜5 with the addition of saturated aq sodium bicarbonate, and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the title compound as an amorphous off-white solid (39%). MS(ES)+ m/e 429.1 [M+H]+.

1. customThe reaction mixture was purged with nitrogen
2. customsealed
3. customirradiated in a microwave (Biotage Initiator) at 150° C. for 15 min
4. additionwas diluted with water (50 mL)
5. extractionwas extracted with dichloromethane
6. additionThe resulting organic phase was treated with Si-Thiol (Silicycle, 20 mg)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude residue was purified by reverse phase HPLC (35-65% acetonitrile w/0.1% TFA/water w/0.1% TFA)
11. additionadjusted to pH˜5 with the addition of saturated aq sodium bicarbonate
12. extractionextracted with dichloromethane
13. dry with materialThe organic layer was dried over magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated in vacuo